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To examine the relationship between infection with Toxoplasma gondii (toxo) and cognition. Multivariate logistic regression was used to test the association of toxo seropositivity with indices of cognitive function among over 4,200 adults in the third National Health and Nutrition Examination Survey. Toxo-seropositive participants were more likely than seronegative participants to score in the worst quartile of the simple reaction time test (OR 1.3, 95 % CI 1.0, 1.6), symbol-digit substitution test (SDST, OR 1.5, 95 % CI 1.2, 1.9) and the serial-digit learning test (trials to criterion) (SDLTNT, OR 1.4, 95 % CI 1.1, 1.8) in models adjusted for age, race/ethnicity, gender and foreign birth. After further adjustment for all cofactors, the association between toxo seropositivity and these outcomes was no longer significant. However, seropositivity was associated with worse scores on the SDST (OR 2.9, 95 % CI 1.8, 4.8) among those in the lowest income category and the SDLTNT (OR 1.5, 95 % CI 1.1, 2.5) among those foreign born. Toxo seropositivity may be associated with poor cognitive test scores in certain subgroups; however, causation cannot be established in this cross-sectional study.